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Impaired immunosuppressive role of myeloid-derived suppressor cells in acquired aplastic anemia
Myeloid-derived suppressor cells (MDSC) are a group of heterogeneous immature myeloid cells and display immunosuppressive function. In this study, MDSC populations were evaluated in acquired aplastic anemia (AA) (n=65) in which aberrant immune mechanisms contributed to bone marrow destruction. Our d...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Fondazione Ferrata Storti
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9713570/ https://www.ncbi.nlm.nih.gov/pubmed/35734923 http://dx.doi.org/10.3324/haematol.2021.280292 |
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author | Dong, Peiyuan Chen, Lingyun Wu, Hongfei Huo, Jiali Jiang, Zhongxing Shao, Yingqi Ren, Xiang Huang, Jinbo Li, Xingxin Wang, Min Nie, Neng Zhang, Jing Jin, Peng Zheng, Yizhou Ge, Meili |
author_facet | Dong, Peiyuan Chen, Lingyun Wu, Hongfei Huo, Jiali Jiang, Zhongxing Shao, Yingqi Ren, Xiang Huang, Jinbo Li, Xingxin Wang, Min Nie, Neng Zhang, Jing Jin, Peng Zheng, Yizhou Ge, Meili |
author_sort | Dong, Peiyuan |
collection | PubMed |
description | Myeloid-derived suppressor cells (MDSC) are a group of heterogeneous immature myeloid cells and display immunosuppressive function. In this study, MDSC populations were evaluated in acquired aplastic anemia (AA) (n=65) in which aberrant immune mechanisms contributed to bone marrow destruction. Our data demonstrate that both the proportion and immunosuppressive function of MDSC are impaired in AA patients. Decreased percentage of MDSC, especially monocytic MDSC, in the blood of AA patients (n=15) is positively correlated with the frequency of T-regulatory cells, bone marrow level of WT1 and decreased plasma level of arginase-1. RNA sequencing analyses reveal that multiple pathways including DNA damage, interleukin 4, apoptosis, and Jak kinase singnal transducer and activator of transcription are upregulated, whereas transcription, IL-6, IL-18, glycolysis, transforming growth factor and reactive oxygen species are downregulated in MDSC of AA (n=4), compared with that of healthy donors (n=3). These data suggest that AA MDSC are defective. Administration of rapamycin significantly increases the absolute number of MDSC and levels of intracellular enzymes, including arginase-1 and inducible nitric-oxide synthase. Moreover, rapamycin inhibits MDSC from differentiating into mature myeloid cells. These findings reveal that impaired MDSC are involved in the immunopathogenesis of AA. Pharmacologically targeting of MDSC by rapamycin might provide a promising therapeutic strategy for AA. |
format | Online Article Text |
id | pubmed-9713570 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Fondazione Ferrata Storti |
record_format | MEDLINE/PubMed |
spelling | pubmed-97135702022-12-12 Impaired immunosuppressive role of myeloid-derived suppressor cells in acquired aplastic anemia Dong, Peiyuan Chen, Lingyun Wu, Hongfei Huo, Jiali Jiang, Zhongxing Shao, Yingqi Ren, Xiang Huang, Jinbo Li, Xingxin Wang, Min Nie, Neng Zhang, Jing Jin, Peng Zheng, Yizhou Ge, Meili Haematologica Article - Bone Marrow Failure Myeloid-derived suppressor cells (MDSC) are a group of heterogeneous immature myeloid cells and display immunosuppressive function. In this study, MDSC populations were evaluated in acquired aplastic anemia (AA) (n=65) in which aberrant immune mechanisms contributed to bone marrow destruction. Our data demonstrate that both the proportion and immunosuppressive function of MDSC are impaired in AA patients. Decreased percentage of MDSC, especially monocytic MDSC, in the blood of AA patients (n=15) is positively correlated with the frequency of T-regulatory cells, bone marrow level of WT1 and decreased plasma level of arginase-1. RNA sequencing analyses reveal that multiple pathways including DNA damage, interleukin 4, apoptosis, and Jak kinase singnal transducer and activator of transcription are upregulated, whereas transcription, IL-6, IL-18, glycolysis, transforming growth factor and reactive oxygen species are downregulated in MDSC of AA (n=4), compared with that of healthy donors (n=3). These data suggest that AA MDSC are defective. Administration of rapamycin significantly increases the absolute number of MDSC and levels of intracellular enzymes, including arginase-1 and inducible nitric-oxide synthase. Moreover, rapamycin inhibits MDSC from differentiating into mature myeloid cells. These findings reveal that impaired MDSC are involved in the immunopathogenesis of AA. Pharmacologically targeting of MDSC by rapamycin might provide a promising therapeutic strategy for AA. Fondazione Ferrata Storti 2022-06-23 /pmc/articles/PMC9713570/ /pubmed/35734923 http://dx.doi.org/10.3324/haematol.2021.280292 Text en Copyright© 2022 Ferrata Storti Foundation https://creativecommons.org/licenses/by-nc/4.0/This article is distributed under the terms of the Creative Commons Attribution Noncommercial License (by-nc 4.0) which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited. |
spellingShingle | Article - Bone Marrow Failure Dong, Peiyuan Chen, Lingyun Wu, Hongfei Huo, Jiali Jiang, Zhongxing Shao, Yingqi Ren, Xiang Huang, Jinbo Li, Xingxin Wang, Min Nie, Neng Zhang, Jing Jin, Peng Zheng, Yizhou Ge, Meili Impaired immunosuppressive role of myeloid-derived suppressor cells in acquired aplastic anemia |
title | Impaired immunosuppressive role of myeloid-derived suppressor cells in acquired aplastic anemia |
title_full | Impaired immunosuppressive role of myeloid-derived suppressor cells in acquired aplastic anemia |
title_fullStr | Impaired immunosuppressive role of myeloid-derived suppressor cells in acquired aplastic anemia |
title_full_unstemmed | Impaired immunosuppressive role of myeloid-derived suppressor cells in acquired aplastic anemia |
title_short | Impaired immunosuppressive role of myeloid-derived suppressor cells in acquired aplastic anemia |
title_sort | impaired immunosuppressive role of myeloid-derived suppressor cells in acquired aplastic anemia |
topic | Article - Bone Marrow Failure |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9713570/ https://www.ncbi.nlm.nih.gov/pubmed/35734923 http://dx.doi.org/10.3324/haematol.2021.280292 |
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